Bacteriophages evolve enhanced persistence to a mucosal surface.

Area of Science:

• Microbiology
• Evolutionary Biology
• Gastroenterology

Background:

• Bacteriophages (phages) are bacterial viruses in the gut that coevolve with gut bacteria.
• Previous studies focused on phage-bacteria coevolution using in vitro and in vivo models.
• The role of the mammalian gut mucosa in phage evolution remains underexplored.

Purpose of the Study:

• To investigate tripartite evolutionary interactions between phages, bacteria, and the mammalian gut mucosa.
• To model the gut mucosal environment using lab-on-a-chip technology.
• To understand phage adaptation mechanisms within a mucosal context.

Main Methods:

• Utilized gut-on-a-chip devices to simulate the mammalian gut mucosal layer.
• Experimentally coevolved lytic phage populations with their bacterial hosts in the gut-on-a-chip.
• Analyzed phage adaptation through de novo mutations and genetic recombination.
• Identified specific mutations affecting phage-mucus interactions.

Main Results:

• The gut-on-a-chip model supported stable phage-bacteria coexistence.
• Phages adapted to the mucosal environment primarily through genetic recombination, with de novo mutations also contributing.
• A mutation in the phage Hoc protein altered binding to fucosylated mucin glycans.
• This altered binding phenotype provided a competitive fitness advantage to evolved phages in the mucosal environment.

Conclusions:

• Phages can evolve in response to the mammalian gut mucosal environment, beyond their interactions with bacteria.
• The gut mucosa acts as a selective pressure driving phage adaptation.
• Specific phage adaptations, like altered glycan binding, can enhance survival and competitiveness within the gut ecosystem.